Objective: The objective of this study was to evaluate the performance of surface-enhanced Raman spectroscopy (SERS) in the prediction of early biochemical recurrence after radical prostatectomy (RP).Patients and methods: We synthesized monodisperse gold nanoparticles as SERS-enhanced substrates and analyzed preoperative plasma samples of patients who underwent RP. The roles of clinical risk model (Cancer of the Prostate Risk Assessment [CAPRA] score) and distinctive SERS spectra on prediction of early biochemical recurrence were evaluated. The principal component analysis and linear discriminant analysis (PCA-LDA) were used to manage the spectral data and develop diagnostic algorithm.Results: A total of 306 preoperative plasma Raman spectra from 102 patients were collected. SERS spectrum from those who developed early biochemical recurrence were compared to those who remained biochemical recurrence-free. The SERS detected more abundant circulating free nucleic acid bases in biochemical recurrence population, presenting significant stronger intensities at SERS spectral bands 725 and 1,328 cm-1. The addition of Raman spectral peak 1,328 cm-1 to CAPRA postsurgical (CAPRA-S) score significantly improved the predictive power of logistic regression model compared to simple CAPRA score (P<0.001). Meanwhile, the leave-one-out cross-validation method was used to validate the PCA-LDA model and revealed the sensitivity, specificity, and accuracy of 65.8%, 87.5%, and 79.4%, respectively. The receiver operating characteristic (ROC) curve was used to evaluate the performance of different models. Area under the ROC curve of the CAPRA-S score model alone was 0.77, however, when combined with Raman spectral peak 1,328 cm-1, it improved to 0.81.Conclusion: Our primary results suggested that SERS could be a meaningful technique for prediction of early biochemical recurrence in prostate cancer.

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